A targeting drug delivery system using folate‐conjugated pluronic F127/chitosan core‐shell nanoparticles was developed to deliver doxorubicin (DOX) to the target cancer cells. First, DOX was encapsulated in pluronic F127 micelle cores in the presence of sodium dodecyl sulfate (SDS) by a self‐assembly method. To form a shell, a layer of either chitosan or folate‐conjugated chitosan was deposited onto the pluronic micelles. The encapsulation efficiency was approximately 58.1 ± 4.7%. The average size of the core‐shell nanoparticles was 37.4 ± 2.0 nm, while the zeta potential was 12.9 ± 2.3 mV, indicating the presence of a shell layer and more stable particles. In an in vitro DOX release study, an initial burst release, followed by a sustained release, was observed within 24 hours. In addition, the core‐shell nanoparticles showed greater cytotoxicity towards MCF‐7 cells than free DOX, suggesting a better therapeutic efficacy in treating cancer.
1 June 2019 in International Journal of Nanomedicine
Purpose: Doxorubicin (DOX) encapsulated O-succinyl chitosan graft Pluronic® F127 (OCP) copolymer nanoparticles conjugated with an anti-HER2 monoclonal antibody were developed as targeted drug delivery vehicles for the treatment of HER2-overexpressing breast cancer. Methods: Five percent and 10% (w/w) of O-succinyl chitosan was grafted onto Pluronic® F127 using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) as mediated cross-linking agents. DOX was added to the copolymer solution to form DOX-nanoparticles before conjugation with anti-HER2 on the surface of the nanoparticles. Results: DOX was encapsulated within the NP matrices at an encapsulation efficiency of 73.69 ± 0.53% to 74.65 ± 0.44% (the initial DOX concentration was 5 μg/mL). Anti-HER2 was successfully conjugated onto the surface of the nanoparticles at a moderately high conjugation efficiency of approximately 57.23 ± 0.38% to 61.20 ± 4.42%. In the in vitro DOX dissolution study, the nanoparticle formulations exhibited a biphasic drug release with an initial burst release followed by a sustained release profile at both pH 5.0 and pH 7.4. The drug was rapidly and completely released from the nanoparticles at pH 5.0. In the in vitro cytotoxicity, the anti-HER2 conjugated OCP copolymer nanoparticles showed the lowest IC50, which indicated an increase in the therapeutic efficacy of DOX to treat human breast cancer cells with the HER2 overexpression. Conclusion: Our study shows that anti-HER2 conjugated OCP copolymer nanoparticles have the potential for the development of anticancer drug carriers.
1 October 2009 in International Journal of Pharmaceutics
Poly(N-isopropylacrylamide-co-acrylamide) (PNIAM-co-AM)-grafted surfaces have been reported to promote cell adhesion and detachment by a hydrophobic-to-hydrophilic transition triggered by temperature change. However, the surface uniformity and cell detachment consistency are still an issue. In this study, PNIAM-co-AM is prepared with spin coating to control the grafting density and the thickness and to achieve better cell detachment. The atomic force microscopy results indicate that the surface becomes smoother as the spin speed increases. The attenuated total reflection Fourier transform infrared results show a grafting density from 1.68 to 2.03 μg/cm2. Ellipsometry suggests that the thickness of the spin-coated PNIAM-co-AM layer is 11–21 nm. The grafted surfaces were tested with mouse preosteoblast MC3T3-E1 cells, which grew successfully. The detachment reached 100 percent with the samples prepared with 1.5 and 2 h ultraviolet exposure times without the use of a poly(vinylidene difluoride) membrane. The detached sheet was in good condition, as indicated by Live/Dead stains.
Implantation failure due to bacterial infection incurs significant medical expenditure annually, and treatment tends to be complicated. This study proposes a method to prevent bacterial infection in implants using an antibiotic delivery system consisting of vancomycin loaded into poly-L-lactic acid (PLLA) matrices. A thin layer of this antibiotic-containing polymer was formed on stainless steel surfaces using a simple dip-coating method. SEM images of the polymeric layer revealed a honeycomb structure of the PLLA network with the entrapment of vancomycin molecules inside. In the in vitro release study, a rapid burst release was observed, followed by a sustained release of vancomycin for approximately 3 days. To extend the release time, a drug-free topcoat of PLLA was introduced to provide a diffusion resistance layer. As expected, the formulation with the drug-free topcoat exhibited a significant extension of the release time to approximately three weeks. Furthermore, the bonding strength between the double-layer polymer and the stainless steel substrate, which was an important property reflecting the quality of the coating, significantly increased compared to that of the single layer to the level that met the requirement for medical coating applications. The release profile of vancomycin from the double-layer PLLA film was best fitted with the Korsmeyer–Peppas model, indicating a combination of Fickian diffusion-controlled release and a polymer relaxation mechanism. More importantly, the double-layer vancomycin-PLLA coating exhibited antibacterial activity against S. aureus, as confirmed by the agar diffusion assay, the bacterial survival assay, and the inhibition of bacterial surface colonization without being toxic to normal cells (L929). Our results showed that the proposed antibiotic delivery system using the double-layer PLLA coating is a promising solution to prevent bacterial infection that may occur after orthopedic implantation.